ABSTRACT
Despite preventing death after snakebites, there is little evidence that polyvalent antivenoms (PAVs) protect against myotoxicity and local damages. We evaluated antibothropic Brazilian PAVs from three manufacturers against the myotoxicity and hemorrhagic activity of Bothrops jararacussu and B. jararaca venoms, respectively, by using two protocols: preincubation of PAVs with venom, and i.v. pretreatment with PAVs, prior to the venom inoculation. In this investigation, we used doses of PAVs ranging from 0.4 to 4.0mL/mg of venom equivalent up to 10 times the amount recommended by the producers for the clinical practice in Brazil. In our preincubation protocol in vivo, PAVs antagonized myotoxicity of B. jararacussu venom by 40-95%, while our pretreatment protocol antagonized myotoxic activity by 0-60%. Preincubation of antivenoms with B. jararaca venom antagonized its hemorrhagic activity by 70-95%, while pretreatment antagonized hemorrhagic activity by 10-50%. Although all PAVs demonstrated partial antagonism against both venoms, the magnitude of these effects varied greatly among the manufactures. The results suggest that the current clinical doses of these PAVs may have negligible antimyotoxic effect.
Subject(s)
Antivenins/therapeutic use , Bothrops/physiology , Crotalid Venoms/antagonists & inhibitors , Crotalid Venoms/toxicity , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Muscular Diseases/prevention & control , Animals , Brazil , Crotalid Venoms/enzymology , Enzyme Inhibitors/pharmacology , In Vitro Techniques , Mice , Muscular Diseases/chemically induced , Muscular Diseases/pathology , Necrosis , Peptide Hydrolases/toxicity , Phospholipases/antagonists & inhibitors , Phospholipases/toxicity , Protease Inhibitors/pharmacologyABSTRACT
Pulmonary mechanics [static (Est) and dynamic (Edyn) elastances, resistive (DeltaP1) and viscoelastic pressures (DeltaP2)], histology, and bronchoalveolar lavage fluid (BALF) from BALB/c mice were analysed 1, 24, 48 and 72 h after intravenous injection of saline or Bothrops jararaca crude venom [0.3 (V0.3) or 1 (V1) microg.g(-1)]. Est, Edyn, and DeltaP2 increased at 1 h in both V groups, being significantly higher in V1 than in V0.3, decreasing progressively, reaching control values at 48 h in V0.3, but remaining altered in V1 at 72 h. DeltaP1 augmented in V1 at 1 h, returning to normal at 72 h. Histological changes in V0.3 group included interstitial oedema, alveolar collapse, and increased cellularity, which returned to normal at 48 h. These changes were more intense in V1 group, with alveolar oedema and haemorrhage. BALF showed time-dependent neutrophil influx in V0.3. In conclusion, venom led to time- and dose-dependent pulmonary mechanical changes, together with moderate inflammation in V0.3 and acute lung injury in V1.
Subject(s)
Bothrops , Crotalid Venoms/toxicity , Respiratory Distress Syndrome , Respiratory Mechanics/drug effects , Animals , Bothrops/metabolism , Bronchoalveolar Lavage Fluid , Cell Count , Histology , Mice , Mice, Inbred BALB C , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/physiopathology , Time FactorsABSTRACT
Seven new 1,4-naphthoquinones structurally related to lapachol were synthesized from lawsone and oxygenated arylmercurials. These compounds can also be seen as pterocarpan derivatives where the A-ring was substituted by the 1,4-naphthoquinone nucleus. Pharmacological screening provided evidence of significant biological activities, including effects against proliferation of the MCF-7 human breast cancer cell line, against Herpes Simplex Virus type 2 infection, and against snake poison-induced myotoxicity. One derivative displaced flunitrazepam binding and showed benzodiazepine-like activity, suggesting novel neuroactive structural motifs.
